Direct Lentiviral Injection Gene Therapy for MLD

NCT03725670 | Recruiting

• 1 other identifier: GIMI-IRB-18005
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II clinical trial of gene therapy for treating Metachromatic leukodystrophy (MLD) using a safety and efficacy improved self-inactivating lentiviral vector TYF-ARSA to functionally correct the genetic defect. The primary objectives are to evaluate the safety and efficacy of the direct gene transfer clinical protocol.

Conditions

Metachromatic Leukodystrophy (MLD)

Keywords

Metachromatic leukodystrophy (MLD); lentiviral vector; Intrathecal injection; Intravenous injection

Outcome Measures

Primary Outcomes (3)

• Safety of IT and IV injections of lentiviral TYF-ARSA

  Safety of IT and IV injections of lentiviral TYF-ARSA, determined by number of participants with treatment-related adverse events (AEs), according to scheduled assessments, vital signs, \& physical examinations as assessed by CTCAE v4.0. AEs \& clinically significant abnormalities (meeting grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity \& relationship to the study drug(s). The grade of AEs will be summarized if related to the treatment.

  up to 1 year follow up

• Altered disease progression

  Altered disease progression based on biochemical analysis.

  up to 3 year follow up after treatment

• Altered disease progression

  Altered disease progression based on MRI brain imaging analysis

  up to 3 year follow up after treatment

Study Arms (1)

Lentivirus-mediated delivery of ARSA to the CNS and the body

EXPERIMENTAL

Intrathecal and intravenous injections with lentiviral TYF-ARSA vector carrying the functional gene

Genetic: Intrathecal and intravenous LV gene therapy

Interventions

Intrathecal and intravenous LV gene therapy GENETIC

Direct IT and IV LV gene therapy to deliver high levels of LVs at 1-2×10\^9 transduction units/ml which carry a normal ARSA gene

Lentivirus-mediated delivery of ARSA to the CNS and the body

Eligibility Criteria

• Age: 1 Month - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• MLD patient age \>= 1 month
• ARSA gene sequence analysis to confirm MLD mutations
• Scoring system for brain MR Imaging confirmed MLD
• Parent / guardian / patient signing informed consent
• Patients and their families have a strong willingness to participate in clinical trials, and are willing to bear all the consequences caused by the failure of the trial, and sign an informed consent form

You may not qualify if:

• HIV positive patients
• Patients who are experiencing uncontrolled viral, bacterial or fungal infections, malignant tumors, heart abnormalities, liver dysfunction, or renal insufficiency
• Cannot perform an MRI
• Infection or dermatosis at pre-injection site
• Any condition that may increase the subjects' risk or interfere with the results of the trial. In addition to MLD, there are other neurological disorders.

Sponsors & Collaborators

• Shenzhen Geno-Immune Medical Institute: lead

Study Sites (1)

Lung-Ji Chang

Shenzhen, Guangdong, 518000, China

RECRUITING

MeSH Terms

Conditions

Leukodystrophy, Metachromatic

Condition Hierarchy (Ancestors)

Hereditary Central Nervous System Demyelinating Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sulfatidosis; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Leukoencephalopathies; Demyelinating Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Lung-Ji Chang, Ph.D

  Shenzhen Geno-Immune Medical Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lung-Ji Chang, Ph.D

CONTACT

+86 0755-86573763; c@szgimi.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: October 31, 2018
• Study Start: May 31, 2025
• Primary Completion: May 31, 2025
• Study Completion (Estimated): December 31, 2030
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)